The long-range goal of the proposed research is to achieve an understanding at the molecular level of the functions of immunoglobulins. To this end we have focused our attention on the structure and biosynthesis of membrane Ig, T cell antigen receptors and Fc receptors. Using similar methodologies we will also study the aberrations of Ig structure and biosynthesis that may exist in leukemic lymphocytes. It is anticipated that the information obtained will contribute to the understanding of mechanisms by which antigen triggers lymphocyte proliferation and differentiation. The proposal has three distinct but related areas of research: 1) The structure and biosynthesis of membrane immunoglobulin and secreted immunoglobulin in normal and in leukemic lymphocytes. The structural features of membrane immunoglobulins responsible for integration into the plasma membrane will be investigated by radioisotope and microsequencing techniques. The biosynthetic pathways of membrane IgM and IgD and of the secreted forms of these immunoglobulins will be examined using biosynthetic labeling methods on intact cells and in a cell-free system. Intracellular trafficking and post-translational modification events will be studied by biochemical and ultrastructural analyses. Similar methods will be utilized to examine the possible cellular and/or immunoglobulin structural defects with the inability of leukemic lymphocytes to secrete intact immunoglobulins. 2) The nature of T cell antigen receptors in contact sensitivity. The antigen receptor on T lymphocytes responsible for delayed type hypersensitivity to the contactant DNFB will be isolated and characterized using affinity methods dependent upon the capacity of the receptor to bind antigen, anti-idiotype and anti-V(H) framework reagents. 3) The structure and function of Fc receptors on lymphocytes and macrophages. The functional studies that will be examined include the regulation of immunoglobulin secretion by plasma cells, the regulatory role of Fc receptors on B cell differentiation, the mechanism of immunoglobulin transport across gut epithelium, and the interaction of Fc receptors with intracellular cytoskeletal elements.